Encephalitis lethargica
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Encephalitis lethargica (EL) is an atypical form of encephalitis. Also known as "von Economo Encephalitis", "sleeping sickness" or "sleepy sickness" (distinct from tsetse fly–transmitted sleeping sickness), it was first described in 1917 by neurologist Constantin von Economo<ref>Template:WhoNamedIt</ref><ref>Template:Cite journal</ref> and pathologist Jean-René Cruchet.<ref>Template:Cite journal</ref> The disease attacks the brain, leaving some victims in a statue-like condition, speechless and motionless.<ref name=Dale_2004>Template:Cite journal</ref> Between 1915 and 1926,<ref>Template:DorlandsDict</ref> an epidemic of encephalitis lethargica spread around the world. The exact number of people infected is unknown, but it is estimated that more than one million people contracted the disease during the epidemic, which directly caused more than 500,000 deaths.<ref name=Ravenholt-Foege-1982>Template:Cite journal</ref><ref name=McCall-Vilensky-etal-2008>Template:Cite journal</ref><ref name=Hoffman-Vilensky-etal-2017>Template:Cite journal</ref> Most of those who survived never recovered their pre-morbid vigour.
Signs and symptoms
Encephalitis lethargica is characterized by high fever, sore throat, headache, lethargy, double vision, delayed physical and mental response, sleep inversion and catatonia.<ref name=Dale_2004/><ref>Template:Cite magazine</ref> In severe cases, patients may enter a coma-like state (akinetic mutism).Template:Citation needed Patients may also experience abnormal eye movements ("oculogyric crises"),<ref name=pmid16200538> Template:Cite journal </ref> Parkinsonism, upper body weakness, muscular pains, tremors, neck rigidity, and behavioral changes including psychosis.Template:Citation needed Klazomania, a vocal tic involving compulsive screaming, is sometimes present.<ref name=Jankovic>Template:Cite journal</ref>
Approximately a third of the affected children experienced change of behavior, with many of them becoming "delinquents".<ref>Template:Cite journal</ref> Boys between the ages of 5 and 18 years were the most affected. Symptoms include change of personality, restlessness, irregular sleeping habits, emotional instability manifesting as irritability, crying spells, and temper tantrums, including impulsivity, and unpredictability, what Economo described as "moral insanity". More extreme cases include aggression and "shameless sexual activity". Children under the age of 5 years suffered severe developmental delays. Delays were also present in children between 5 and 14 years of age, even though the claims are controversial.<ref name="archives">Template:Cite journal</ref>
It is estimated that 25–90% of adults also suffered from psychological problems, including hysteria and abnormal behavior and movement. A large minority of patients described having bradyphrenia.<ref name="archives"/>
Cause
The causes of encephalitis lethargica are uncertain.<ref name=McCall-Vilensky-etal-2008/><ref name=EncphSoc-2017>Template:Cite web</ref> Though it used to be believed that it was connected to the Spanish flu epidemic, modern research provides arguments against this claim.<ref name=Reid-McCall-etal-2001/> Some studies have explored its origins in an autoimmune response,<ref name=Dale_2004/> and, separately or with an immune response, links to pathologies of infectious disease – viral and bacterial,<ref name=Dale_2004/> such as in the case of influenza, where a link with encephalitis is clear.<ref name= Haeman> Template:Cite journal </ref> Postencephalitic Parkinsonism was clearly documented to have followed an outbreak of encephalitis lethargica following the 1918 influenza pandemic; evidence for viral causation of the Parkinson's symptoms is circumstantial (epidemiologic, and finding influenza antigens in encephalitis lethargica patients), while evidence arguing against this cause is of the negative sort (for example, lack of viral RNA in postencephalitic Parkinsonian brain material).<ref name=Haeman/>
In reviewing the relationship between influenza and encephalitis lethargica (EL), McCall and co-authors conclude, as of 2008, that "the case against influenza [is] less decisive than currently perceived ... [yet] there is little direct evidence supporting influenza in the etiology of EL," and that "[a]lmost 100 years after the EL epidemic, its etiology remains enigmatic."<ref name=Reid-McCall-etal-2001> Template:Cite journal </ref> Hence, while opinions on the relationship of encephalitis lethargica to influenza remain divided, the preponderance of literature appears skeptical.<ref name=Reid-McCall-etal-2001/><ref name=pmid17675021> Template:Cite journal </ref>
The German neurologist Template:Ill, who examined hundreds of encephalitis lethargica patients during the 1920s, noted that their encephalitis lethargica typically evolved over time:
- The early symptoms would be dominated by sleepiness or wakefulness.
- A second symptom would lead to an oculogyric crisis.
- The third symptom would be recovery, followed by a Parkinson-like syndrome.
If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, but had no evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is the author of the definitive book, Template:Lang.<ref> Template:Cite news </ref>
In 2010, in a substantial compendium<ref name=Vilensky-etal-2010/> reviewing the historic and contemporary views on EL, it quotes a researcher, writing in 1930, who stated, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved", and went on to offer the following conclusion, as of that publication date: Template:Quote
After the publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic.<ref> Template:Cite journal </ref> In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease.<ref> Template:Cite letter </ref>Template:Verify inline Other sources have suggested Streptococcus pneumoniae as a cause.<ref> Template:Cite news </ref>
Diagnosis
There have been several proposed diagnostic criteria for encephalitis lethargica. One, which has been widely accepted, includes an acute or subacute encephalitic illness where all other known causes of encephalitis have been excluded. Another diagnostic criterion, suggested more recently, says that the diagnosis of encephalitis lethargica "may be considered if the patient's condition cannot be attributed to any other known neurological condition and that they show the following signs: influenza-like signs; hypersomnolence (hypersomnia), wakeability, ophthalmoplegia (paralysis of the muscles that control the movement of the eye), and psychiatric changes".<ref> Template:Cite web </ref> Others describe lethargy, "mask-like faces", excess blood in the meninges, and other general neurological symptoms.<ref name=Hoffman-Vilensky-2017> Template:Cite journal </ref>
Treatment
Modern treatment approaches to encephalitis lethargica include immunomodulating therapies and treatments to remediate specific symptoms.<ref> Template:Cite journal </ref>
There is little evidence so far of a consistent effective treatment for the initial stages, though some patients given steroids have seen improvement.<ref name=Blunt_1997>Template:Cite journal</ref> The disease becomes progressive, with evidence of brain damage similar to that of Parkinson's disease.<ref>Template:Cite journal</ref>Template:Update after
Treatment is then symptomatic. L-DOPA (Levodopa) and other anti-Parkinson drugs often produce dramatic responses; however, most people given L-DOPA experience improvements that are short-lived.<ref>Template:Cite web</ref><ref name=Sacks-1990-np>Template:HarvpTemplate:Page needed</ref>
History
Occurrences
Retrospective diagnosis tentatively suggests various historical outbreaks of encephalitis lethargica:
- In 1580, Europe was swept by a serious febrile and lethargic illness that led to Parkinsonism and other neurological sequelae.<ref name=Sacks-1990-p319>Template:Harvp</ref>
- From 1673 to 1675, a similar serious epidemic occurred in London, which Thomas Sydenham described as Template:Lang.<ref name=Sacks-1990-p319/>
- In 1695, a 20-year-old woman in Germany experienced oculogyric crises, Parkinsonism, diplopia, strabismus, and other symptoms following an attack of somnolent brain fever, as described by Albrecht of Hildesheim.<ref name=Sacks-1990-p319/>
- In 1712–1713, a severe epidemic of Template:Lang ('sleep sickness') occurred in Tübingen, Germany, followed in many cases by persistent slowness of movement and lack of initiative (aboulia).<ref name=Sacks-1990-p319/>
- Between 1750 and 1800, France and Germany experienced minor epidemics of Template:Lang with features of Parkinsonism, including hyperkinetic hiccup, myoclonus, chorea, and tics.
- Between 1848 and 1882, Paris-based neurologist Jean-Martin Charcot documented many isolated cases of juvenile Parkinsonism, associated with diplopia, oculogyria, tachypnoea, retropulsion, and obsessional disorders, which were almost certainly post-encephalitic in origin.<ref name=Sacks-1990-p319/>
- In 1890 in Italy, following the influenza epidemic of 1889–1890, a severe epidemic of somnolent illnesses (nicknamed the "Nona") appeared. For the few survivors of the Nona, Parkinsonism and other sequelae developed in almost all cases.<ref name=Sacks-1990-p319/>
- Between 1915 and 1927, a world-wide encephalitis lethargica pandemic occurred, impacting nearly 5 million people and killing an estimated 1.6 million people.<ref name=Sacks-1990-p319/>
Pandemic of 1915–1927
Template:Further In the winter of 1916–1917, a "new" illness suddenly appeared in Vienna and other cities, and rapidly spread worldwide over the next three years. Earlier reports appeared throughout Europe as early as the winter of 1915–1916, but communication about the disease was slow and chaotic, given the varied manifestation of symptoms and difficulties disseminating information in wartime;<ref name=Sacks-1990-p12>Template:Harvp</ref> it was officially recognized as a distinct disease in 1917.<ref name=Hoffman-Vilensky-2017/> Some authors define the span of the outbreak as being from 1918 to 1930.<ref name=Dourmashkin-1997>Template:Cite journal</ref>
Neurologist Constantin von Economo published a paper in April 1917 describing some of the cases he encountered in the winter months of 1916–1917.<ref name=Reid-McCall-etal-2001/> These patients, despite varying diagnoses, had a similar pattern of symptoms which led von Economo to suggest a novel disease, which he called Encephalitis Lethargica.<ref name=Reid-McCall-etal-2001/> In France, physician Jean-René Cruchet was experiencing something similar, and he published his findings within a few days of von Economo.<ref name=Reid-McCall-etal-2001/>After these two, many more reports began being released about the disease, starting in Europe before moving around the globe.<ref name=Hoffman-Vilensky-2017/>
Until Constantin von Economo identified a unique pattern of damage among the brains of deceased patients and introduced the unifying name encephalitis lethargica, reports of the protean disease came in under a range of names: botulism, toxic ophthalmoplegia, epidemic stupor, epidemic lethargic encephalitis, acute polioencephalitis, Heine-Medin disease, bulbar paralysis, hystero-epilepsy, acute dementia, and sometimes just "an obscure disease with cerebral symptoms".<ref name=Sacks-1990-p12/> Just 10 days before von Economo's breakthrough in Vienna, Jean-René Cruchet described 40 cases of "subacute encephalomyelitis" in France.<ref name=Sacks-1990-p12/>
The number of people infected during the ten years of the pandemic is unknown, but it is estimated that more than 1 million people contracted the disease, which directly caused more than 500,000 deaths.<ref name=Ravenholt-Foege-1982/><ref name=McCall-Vilensky-etal-2008/><ref name=Hoffman-Vilensky-etal-2017/> Encephalitis lethargica assumed its most virulent form between October 1918 and January 1919.
In the United States, the epidemic peaked from 1920 to 1924.<ref name=Dourmashkin-1997/> It is estimated that as many as one million people were diagnosed with encephalitis lethargica during the epidemic period.<ref name=Hoffman-Vilensky-2017/>
The pandemic disappeared in 1927, as abruptly and mysteriously as it first appeared.<ref name=Sacks-1990-p12/> The great encephalitis pandemic coincided with the 1918 influenza pandemic, and the influenza virus likely potentiated the effects of the causative agent of the encephalitis or lowered resistance to it in a catastrophic way.<ref name=Sacks-1990-p12/>
Aftermath
Many survivors of the 1915–1927 pandemic seemed to make a complete recovery and return to their normal lives. However, the majority of survivors subsequently developed neurological or psychiatric disorders, often after years or decades of seemingly perfect health.
Post-encephalitic syndromes varied widely: sometimes they proceeded rapidly, leading to profound disability or death; sometimes very slowly; sometimes they progressed to a certain point and then stayed at this point for years or decades; and sometimes, following their initial onslaught, they remitted and disappeared.<ref>Template:Harvp</ref> It is also known to cause postencephalitic parkinsonism (PEP).<ref name=Reid-McCall-etal-2001/> Though often thought of as a disease of the past, it is still seen in occasional cases today.<ref name=EncphSoc-2017/>
Notable cases
Notable cases include:
- Muriel "Kit" Richardson (née Hewitt), first wife of actor Sir Ralph Richardson, died of the condition in October 1942, having first shown symptoms in 1927–1928.Template:Citation needed
- There is speculation that Adolf Hitler may have had encephalitis lethargica when he was a young adult (in addition to the more substantial case for Parkinsonism in his later years).<ref>
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- Mervyn Peake (1911–1968), author of the Gormenghast books, began his decline towards death which was initially attributed to encephalitis lethargica with Parkinson's disease–like symptoms, although others have later suggested his decline in health and eventual death may have been due to Lewy body dementia.<ref name=dlb>
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- Those described in the book Awakenings by the British neurologist Oliver Sacks.<ref> Template:Harvp </ref>
- Jane Norton Grew Morgan, wife of J. P. Morgan Jr., died of encephalitis lethargica in 1925. At the time, doctors attributed her encephalitis to having contracted influenza during the 1918 pandemic.<ref>
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See also
References
Further reading
- Template:Cite bookTemplate:ISBN?Template:SndDescribes the history of the disease, and the epidemic of the 1920s.
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External links
- Template:NINDS
- Template:Cite news — item about the tracing of the infectious agent in encephalitis lethargica
Template:Medical resources Template:Viral diseases Template:CNS diseases of the nervous system